2'-5'-oligoadenylate synthase 1 ((2-5')oligo(A) synthase 1) (2-5A synthase 1) (EC 2.7.7.84) (E18/E16) (p46/p42 OAS)
1_MMDLR 6_ NTPAK 11_ SLDKF 16_ IEDYL 21_ LPDTC 26_ FRMQI 31_ NHAID 36_ IICGF 41_ LKERC 46_ FRGSS 51_ YPVCV 56_ SKVVK 61_ GGSSG 66_ KGTTL 71_ RGRSD 76_ ADLVV 81_ FLSPL 86_ TTFQD 91_ QLNRR 96_ GEFIQ 101_ EIRRQ 106_ LEACQ 111_ RERAF 116_ SVKFE 121_ VQAPR 126_ WGNPR 131_ ALSFV 136_ LSSLQ 141_ LGEGV 146_ EFDVL 151_ PAFDA 156_ LGQLT 161_ GGYKP 166_ NPQIY 171_ VKLIE 176_ ECTDL 181_ QKEGE 186_ FSTCF 191_ TELQR 196_ DFLKQ 201_ RPTKL 206_ KSLIR 211_ LVKHW 216_ YQNCK 221_ KKLGK 226_ LPPQY 231_ ALELL 236_ TVYAW 241_ ERGSM 246_ KTHFN 251_ TAQGF 256_ RTVLE 261_ LVINY 266_ QQLCI 271_ YWTKY 276_ YDFKN 281_ PIIEK 286_ YLRRQ 291_ LTKPR 296_ PVILD 301_ PADPT 306_ GNLGG 311_ GDPKG 316_ WRQLA 321_ QEAEA 326_ WLNYP 331_ CFKNW 336_ DGSPV 341_ SSWIL 346_ LAESN 351_ SADDE 356_ TDDPR 361_ RYQKY 366_ GYIGT 371_ HEYPH 376_ FSHRP 381_ STLQA 386_ ASTPQ 391_AEEDW
1: Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:34581622). In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication (PubMed:34145065, PubMed:34581622). Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. The secreted form displays antiviral effect against vesicular stomatitis virus (VSV), herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMCV) and stimulates the alternative antiviral pathway independent of RNase L
2: When prenylated at C-terminal, acts as a double-stranded RNA (dsRNA) sensor specifically targeted to membranous replicative organelles in SARS coronavirus-2/SARS-CoV-2 infected cells where it binds to dsRNA structures in the SARS-CoV-2 5'-UTR and initiates a potent block to SARS-CoV-2 replication. Recognizes short stretches of dsRNA and activates RNase L. The binding is remarkably specific, with two conserved stem loops in the SARS-CoV-2 5'- untranslated region (UTR) constituting the principal viral target (PubMed:34581622). The same mechanism is necessary to initiate a block to cardiovirus EMCV (PubMed:34581622)
3: Not prenylated at C-terminal, is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication